Proteolytic profile of cysteine proteases and inhibitors determines tumor cell phenotype in squamous cell carcinoma of the head and neck.

The hypothesis was tested that a specific pattern in the cysteine cathepsin/inhibitor ratio is associated with the development of more aggressive tumor cell phenotypes in squamous cell carcinoma of the head and neck (SCCHN). For this purpose commercially available ELISAs were used to determine the concentrations of cysteine cathepsins B and L and their inhibitors, stefins A and B, in cytosols of nontumorous mucosa and primary tumors from 92 patients. Using the stefin A concentration difference in matched pairs of tissue samples as a stratifying variable, 53 cases were found to be upregulated (higher concentrations in tumor samples than in nontumorous mucosa) and 39 cases downregulated. Disease recurrence was more frequent in the downregulated group than in the upregulated group (35.9% vs 11.3%, p=0.009), which resulted in significantly different 5-year disease-free survival rates (61.2% vs 88%, p=0.004). The consistency of these results was confirmed by repeating the analysis in an independent group of patients (the reference group). The presented results suggest that in patients with SCCHN, specific patterns in the proteolytic profile of cysteine proteases and their inhibitors are associated with the development of distinctly aggressive tumor cell phenotypes and are of prognostic value.